AB-300 / Parkinson's disease apathy
The ability to act is not the same as the drive to begin.
Ariadne Bio is developing AB-300, an investigational serotonergic therapy for apathy in Parkinson's disease.
The serotonin 5-HT2A receptor
AB-300 is investigational. Its safety and efficacy have not been established, and it has not been approved by any regulatory authority.
- Development
- Funded Phase 1b program
- This research is funded in part by The Michael J. Fox Foundation for Parkinson's Research (MJFF, Research Organization Registry (ROR)) through grant MJFF-028323
- Intellectual property
- U.S. composition-of-matter patent
- Granted November 2025
- Next clinical question
- Initial human safety and pharmacokinetics
- Goal: characterize exposure and tolerability.
Status last updated September 2026.
The category
Not simply low mood. Not simply impaired movement.
Apathy is independently associated with functional decline, greater care-partner burden and distress, and higher institutionalization risk. Care partners are often the first to notice, because apathy reduces the drive to seek help.
Apathy is a persistent reduction in motivation and goal-directed behavior. It is one of the most common non-motor features of Parkinson’s disease and one of the least studied.
40%
Approximately 40% of people with Parkinson's disease, roughly 440,000 Americans, experience clinically significant apathy.
den Brok et al., 2015; Parkinson's Foundation
15.6 million
People projected to be living with Parkinson's disease worldwide in 2030.
Su et al., 2025
Apathy in Parkinson's disease
“Half of patients with apathy do not suffer from concomitant depression or cognitive impairment, confirming its status as a separate clinical syndrome in PD.”
- What may be retained
- Capacity, interest and physical ability.
- Why it matters
- Apathy requires its own measurement and its own therapeutic development. It can be assessed with validated clinical scales, and it persists in many patients after motor symptoms are optimized.
Mistaken for
Depression
Motivation can survive low mood. Antidepressants do not reliably treat apathy in Parkinson's disease, and some studies suggest they may worsen it.
Mistaken for
Motor impairment
Motivation can survive impaired movement. Parkinson's therapies treat motor symptoms effectively, but they do not necessarily address apathy.
The program · AB-300
Motor symptoms improve. Apathy often does not.
AB-300 is being developed as an add-on to stable dopaminergic therapy for people whose apathy persists after motor symptoms are treated.
What is being developed?
The molecule
- Investigational oral small molecule
- Partial agonist at the 5-HT2A receptor
- No measurable activity at dopamine receptors or the dopamine transporter in off-target screening
The intended product
- Designed for a non-hallucinogenic profile
- Designed for chronic oral dosing
- Developed as an add-on to stable dopaminergic therapy
Position
- Initial clinical focus: Parkinson's disease with clinically significant apathy
- Potential future indications: apathy in related conditions of brain aging.
- Regulatory: Type B pre-IND meeting with the U.S. Food and Drug Administration completed, 2026
Why this pharmacology?
The serotonin 5-HT2A receptor is one of the most actively investigated targets in psychiatry. Therapies targeting this serotonin receptor are under active clinical investigation across several conditions. Almost all of that work has been done with compounds that produce a profound subjective experience, and that experience is what has kept the receptor inside supervised settings: a clinic, a monitor, a full day for every dose.
AB-300 is designed to engage the same receptor without producing that experience. If it does, the receptor becomes available to a medicine an older adult can take at home for as long as it is needed. That is a different set of conditions from the ones supervised administration can reach.
What must the clinical program establish?
Ariadne is testing two things at once: whether a 5-HT2A partial agonist designed for a non-hallucinogenic profile can be given chronically in Parkinson's disease, and whether it produces a measurable treatment signal in apathy. The staged Phase 1b is built to answer these questions.
AB-300 is investigational and has not been approved by any regulatory authority.
Mechanistic hypothesis; human circuit engagement remains to be established.
Compare administration models
Model under clinical investigation today Supervised administration |
Model AB-300 is designed for Chronic dosing at home |
|
|---|---|---|
| Serotonin receptor | 5-HT2A | 5-HT2A |
| Hallucinogenic effects | Present, and the reason monitoring is required | Designed to be absent |
| Dosing | Intermittent sessions | Daily oral dosing at home |
| Setting | Clinic, monitored for the duration of the dose | Home |
| Accessibility | Limited to patients who can travel to a clinic and be monitored for the duration of every dose | Suited to older adults managing a chronic condition at home, including those with mobility or care-partner constraints |
| Development status | Varies by program | AB-300 is investigational. Phase 1b expected to begin in the second half of 2026. |
Descriptive comparison of administration models. No claim of comparative efficacy or safety is intended or supported. AB-300 has not been administered to humans.
The team
The people building the program.
The team has taken serotonergic compounds through clinical development and run CNS trials to a decision.
Shlomi Raz
Founder and Chief Executive Officer
Ariadne Bio, Inc.
Founder and CEO, Eleusis; President, Beckley Psytech; Goldman Sachs MD. Leads strategy, financing and partnering.
Kostia Adamsky, PhD
Chief Operating Officer
Ariadne Bio, Inc.
20+ years in biopharma; VP Operations, CEO and co-founder across multiple CNS and neurodegeneration companies; PhD, Weizmann Institute. Leads development planning.
Dan Jeffries, PhD
Chief Development Officer
Ariadne Bio, Inc.
Scientist-founder at the intersection of chemistry and venture; former Roivant; PhD Vanderbilt, postdoc Harvard. Leads clinical strategy, CMC and the nonclinical package.
Ken Belotsky
Managing Director
Ariadne Bio GmbH
Founding Partner of Palomar Labs. Serial founder and venture investor with 25+ CNS and neuroscience deals and 3 exits. Resident in Vienna; leads operational project management and vendor coordination.
C. Anthony (Tony) Altar, PhD
Chief Scientific Officer
Ariadne Bio GmbH
Four decades in CNS discovery and early development; Genentech, Roche, Otsuka. Characterised aripiprazole's partial agonism at serotonin receptors. Austrian citizen. Leads in-house scientific and medical R&D.
Robert Schüssler
Managing Director
Ariadne Bio GmbH
Managing director at the company's Austrian seat since September 2025. Thirty years scaling international technology businesses, including senior roles at SAP. Owns Austrian corporate and authority matters and grant administration.
Vesela Gavrailova
Head of Clinical Operations
Ariadne Bio GmbH
Twenty-one years in clinical research, fifteen of them at Boehringer Ingelheim, most recently as global lead for site management and monitoring. Built and led regional monitoring teams covering eight countries from Vienna. Owns clinical operations for the AB-300 program.
Prior roles reflect companies with which team members were affiliated, and are not attributable to Ariadne Bio or its program. The program is advised by an eight-member clinical and scientific advisory group that includes former pharmaceutical R&D leadership.
The evidence, in context
-
den Brok et al., 2015 · Movement Disorders
Apathy in Parkinson's disease: A systematic review and meta-analysis
Read the study PubMed 25787145 -
Cunningham et al., 2023 · ACS Chemical Neuroscience
Pharmacology of non-hallucinogenic 5-HT2A receptor agonists
Read the study PubMed 36521179 -
Su et al., 2025 · BMJ
Projections for prevalence of Parkinson's disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021
Read the study DOI 10.1136/bmj-2024-080952 -
Xu et al., 2026 · Nature
Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling
Read the study DOI 10.1038/s41586-025-10061-7 -
Parkinson's Foundation · Parkinson's Prevalence Project; Marras et al., 2018, npj Parkinson's Disease
An estimated 1.1 million people in the U.S. are living with Parkinson's disease.
View the page Prevalence & Incidence
These publications provide scientific context. Their authors and publishers are not presented as endorsing AB-300.
Resources
Research and resources
The Hidden Epidemic Apathy in Parkinson's Disease, Neurodegeneration, and the Aging Brain
A review of prevalence, functional and economic burden, current management, and why apathy requires its own measurement and its own therapeutic development.
Request the white paper →Palomar Labs Spins Out Ariadne Bio to Target Apathy in Parkinson's Disease, Where No Approved Therapy Exists
Launch announcement covering AB-300, the staged Phase 1b program, and the funding partners supporting it.
Read the announcement →Media enquiries. Tim Ingersoll, Linnden Communications, tim@linndencom.com
Ariadne Bio is a Palomar Labs company.
Ariadne Bio was formed by Palomar Labs and is its first portfolio company.